The principal aim of this work is to test the viability of Blood Oxygenation Level Dependent (BOLD) measurements in human myocardium, an experiment which has seen promising attempts in recent literature. A central challenge to the ~uccess of these experiments has been in the limited scale of the measured effect; this work therefore includes efforts to separate the BOLD effect from noise and confounding signals. BOLD is then measured by intensity in MR images produced using Steady State Free Precession (SSFP) acquisition, weighted by a T2 preparation module to introduce the target contrast. Two modelling sections are included: first, the changes in physiology which influence the signal intensity in the MR images via the T2 dependence; and secondly the factors upon which the preparation depends, which are not entirely limited to the T2 of the tissue. These models are investigated with the aim of increasing the BOLD contrast and removing any other dependencies. An empirical model is shown to be suitable for the relationship between oxygenation and T2, and improvements are suggested and explained by thorough simulation ofthe preparation module. Compensation for a further confounding effect is also investigated: that of the increase in heart rate which accompanies the adenosine infusion used in the BOLD experiment protocol to reveal differences in the response of ischaemic and healthy tissue. The compensation is shown to reduce temporal variance in SI measurements, and to increase the separation between distributions of SI in tissue classes. A process of registration and segmentation is refined for sampling BOLD information from the SS FP images, and tested to show a low failure rate. Finally, the BOLD process is then tested in a set of human subjects including healthy volunteers and patients with coronary artery disease, investigating the consequent difference in tissue oxygenation. A significant difference is shown in the responses to stress of BOLD SI three tissue classes in these subjects.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Physiology. Title from pdf file main screen (viewed on February 16, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1971. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

This investigation studied the physiological means by which myocardium can survive and function properly when oxygen supply is limited and cannot initially match oxygen demand. The effects of isoproterenol (ISO) stimulations during low coronary perfusion pressure or hypoxemia on myocardial oxygen demand, work, and oxygen utilization efficiency were investigated.

Thesis (Ph. D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on Jan. 18, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Biochemistry, University of Alberta. Includes bibliographical references.

Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease due to poor cell viability in the diseased microenvironment. Genetic manipulation on the MSCs holds promising prospects in enhancing cell tolerance against adverse environmental conditions. Recent studies demonstrate that the activation of the NRG1 (neuregulin 1) - ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) pathway can enhance pro-survival signaling, stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this study, I aimed to determine whether activating NRG1-ERBB4 in MSCs can enhance their cardioprotective effects following myocardial infarction. In chapter 3, I determined that MSC endogenously expresses NRG1, but not ERBB4. Considering the absence of ERBB4 in the MSCs might lead to mute response to its ligand NRG1, I exogenously manipulated ERBB4 into MSCs. In chapter 4, MSCs, with or without ERBB4 overexpression were transplanted into mice following myocardial infarction. The transplantation of MSCs with ERBB4 expression considerably improved left ventricular ejection fraction and reduced infarctsize, compared to unmodified MSCs and direct NRG1 injection. ERBB4 overexpression induced greater MSC survival following infarction. The transduction of ERBB4 in MSCs increased cell mobility and apoptotic resistance via a PI3K/Akt pathway under hypoxic conditions in the presence of NRG1. The transplantation of MSCs with ERBB4 expression induced cardiomyocyte division and protected them against apoptosis during early phase of infarction. In chapter 5, a novel autocrine loop regarding to NRG1-ERBB4-NRG1 signaling was identified. MSCs with ERBB4 overexpression in turn increased NRG1 synthesis and secretion. Conditioned medium of ERBB4-expressing MSCs containing elevated NRG1, promoted cardiomyocyte growth, division and anti-senescence, whereas neutralization of NRG1 blunted these effects. Injecting ERBB4-expressing MSCs restored NRG1 in the infarcted myocardium to a level comparable with that of the normal myocardium. These findings collectively suggest overexpressing ERBB4 in MSCs enhances the effectiveness of MSCtherapy following myocardial in farction through potentiating MSC survival and revitalizing endogenous repair and regeneration. The combination of ERBB4 and MSC is more efficient than naïve MSC or solely recombinant NRG1 injection, emerging as potential target for developing novel strategy in treating myocardial diseases. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

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Proefschrift--Utrecht. / "Stellingen": [2] p. inserted. Summary in Dutch. Bibliography: p. 115-120.

Thesis (M. Med. Sc.)--University of Hong Kong, 200.